The existence of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) continues to be questioned. Confirmation of a relationship of this putative subtype of obsessive compulsive disorder (OCD) and Tourette's Syndrome (TS) to an antecedent Group A Streptococcal (GAS) has gained considerable practical importance because of implications for treatment and prevention interventions that are radically different from the standard practice of administering psychotropics (such as SRIs or neuroleptics) for symptomatic relief. In particular, a study showing the efficacy of plasmapheresis and intravenous immunoglobulin treatment in PANDAS has stimulated public and professional debate, with some parents demanding these interventions for their children and most clinician-scientists urging caution. The need for further research is clear, but no one study will address all the questions surrounding PANDAS. A series of studies designed to test specific aspects of the pathogen-triggered autoimmune hypothesis will be required. The primary specific aim of the present study is to evaluate whether episodes or exacerbations in obsessive-compulsive (OC) or tic symptoms in children with OCD or TS are significantly associated with antecedent GAS infection, as reflected in elevated serum antibody titers. Seventy-nine children (ages 4 to 12 years) with OCD, TS, or Chronic Multiple Tic Disorder (CMT) will participate in this study and be followed for approximately two and a half years, a 28-month period, at monthly intervals for clinical ratings of neuropsychiatric symptoms and serological testing for GAS infection (ASO and AntiDNAse B). The study will be conducted at two institutions, the University of Florida and the National Institute of Mental Health, using identical designs and procedures. In order to identify a cohort that exhibits the desired pattern of exacerbation/regression of symptoms and to allow for attrition, we estimate that approximately 180 patients will have to be enrolled over the five-year study. Blood samples will be obtained at each visit for GAS antibodies and for exploratory immunologic studies. Should clinical signs of pharyngitis develop, throat cultures will be ordered and, if positive for GAS, appropriate antibiotic treatment will be instituted. These cases, estimated at n = 45, may provide useful information on the effect of antibiotics to attenuate exacerbations or influence OC/tic symptom course. In this cohort with clinical GAS pharyngitis, the rate of exacerbations for the 6-months following treatment will be compared to the corresponding period prior to treatment. The proposed longitudinal study will furnish needed data on the validity of the PANDAS concept and help generate reliable operational criteria for identifying cases at risk of GAS-triggered OC or tic symptoms. The results will help determine if antimicrobial interventions are warranted in certain subtypes of pediatric OCD or TS.